End-stage renal disease (ESRD) incidence and prevalence have been increasing relentlessly as long as national statistics have been available. In 1990, over 200,000 people received treatment for ESRD with direct costs of 7.3 billion dollars/1. For the past decade the incidence of ESRD has been increasing at an annual rate of 7.8% with diabetic and hypertensive patients accounting for a large proportion of this increase. Despite these statistics, there are few large prospective studies and the epidemiology of ESRD and renal disease progression is poorly understood. The aim of the two proposed complimentary studies is to identify risk factors of renal disease. During the past year, the investigators completed one of the specific aims proposed for each study. The first study will examine the risk factors for elevated plasma creatinine concentration, [Cr], in the Atherosclerosis Risk in Communities Study (ARIC). ARIC is a population-based, prospective study of 11,475 white and 4,260 African-American men and women aged 45-64 years drawn from four United States Communities. ARIC collected behavioral and biologic data, at baseline and at follow-up every three years. [Cr] was measured at the baseline and 3-year follow-up. This data will be used to examine the risk factors for prevalent and incident "definite hypercreatinemia" (defined as [Cr] greater than 1.6 mg/dl for men and [Cr] greater than 1.4 mg/dl for women). Preliminary work shows that the associations seen with hypercreatinemia in this study are consistent with studies of ESRD. [Cr] will be measured again during the 9-year follow-up visit (1996-1999). This should provide a large number of incident cases of definite hypercreatinemia which will allow for the study risk factors for renal disease progression in more detail. The second study will complement the first by employing a nested case- control design to study serologic risk factors for ESRD. The Health Care Financing Administration database was used to identify 81 incident cases of treated ESRD among 25,000 CLUE participants who donated blood in 1974. The median year of ESRD onset was 1989, providing a median of 15 years of follow-up. Using serum stored at -70 degrees C, we will study the role of antioxidants, lipids, and nitric oxide as well as other factors in predicting the risk of developing ESRD while controlling for the degree of renal insufficiency at baseline. Preliminary analyses indicate that associations in this study are consistent with other case control studies of ESRD. This proposal study builds on two large epidemiologic projects to enhance the limited knowledge of risk factors for ESRD. These investigations will help the FIRST award candidate start a career devoted to the epidemiologic study of renal disease and its primary prevention.